Journal Article

Dynamics of SARS-CoV-2 VOC Neutralization and Novel mAb Reveal Protection against Omicron

Tilles, Sasha, Huden, Kristen, Van Voorhis, Wesley C., Hale, Malika, Gale, Michael, Scobey, Trevor, Wald, Anna, Greninger, Alex L., Drain, Paul K., Netland, Jason, Chu, Helen Y., Rawlings, David J., Dalmat, Ronit R., Pepper, Marion, Morton, Jennifer F., Barrett, Lynn K., Stokes, Caleb, Hao, Linhui, Thouvenel, Chris, Sigal, Alex, Baric, Ralph S., Ireton, Renee, Franko, Nicholas M., Munt, Jennifer, Hsiang, Tien-Ying

2023

Overview

New variants of SARS-CoV-2 continue to emerge and evade immunity. We isolated SARS-CoV-2 temporally across the pandemic starting with the first emergence of the virus in the western hemisphere and evaluated the immune escape among variants. A clinic-to-lab viral isolation and characterization pipeline was established to rapidly isolate, sequence, and characterize SARS-CoV-2 variants. A virus neutralization assay was applied to quantitate humoral immunity from infection and/or vaccination. A panel of novel monoclonal antibodies was evaluated for antiviral efficacy. We directly compared all variants, showing that convalescence greater than 5 months post-symptom onset from ancestral virus provides little protection against SARS-CoV-2 variants. Vaccination enhances immunity against viral variants, except for Omicron BA.1, while a three-dose vaccine regimen provides over 50-fold enhanced protection against Omicron BA.1 compared to a two-dose. A novel Mab neutralizes Omicron BA.1 and BA.2 variants better than the clinically approved Mabs, although neither can neutralize Omicron BA.4 or BA.5. Thus, the need remains for continued vaccination-booster efforts, with innovation for vaccine and Mab improvement for broadly neutralizing activity. The usefulness of specific Mab applications links with the window of clinical opportunity when a cognate viral variant is present in the infected population.

• Publisher: MDPI AG,MDPI
• Subject: Antibodies, Monoclonal / Antiviral Agents / Antiviral drugs / Convalescence / Coronaviruses / COVID-19 - prevention & control / COVID-19 vaccines / Disease transmission / Dosage and administration / Humans / Humoral immunity / Infections / Monoclonal antibodies / monoclonal antibody / neutralization / neutralization assay / neutralization tests / Omicron / pandemic / Pandemics / Phylogenetics / Proteins / Regression analysis / SARS-CoV-2 - genetics / SARS-CoV-2 variant / Severe acute respiratory syndrome coronavirus 2 / Testing / vaccination / Vaccines / Viruses